PROJECT SUMMARY: Control of muscle proprioceptor sensitivity. Complex motor behaviors rely on a constantly updated sense of body position in space, or proprioception. Sensory input from many systems are integrated during proper proprioception, but sensory neurons found in muscles, known as muscle spindle afferents, seem to be the most important. These neurons sense muscle stretch and movement, information that is critical for creating a body schema, coordinated movement, and correcting errors during motor execution. Proprioceptor function is impaired in many conditions, including aging and diabetes, causing balance instability and falls. Fall related injuries are costly and decrease life expectancy. A better understanding of how muscle proprioceptors are regulated under normal circumstances and disease states is needed to develop therapies to improve their function. In this proposal, we will test the hypothesis that proprioceptor released glutamate is essential for proper stretch sensitivity in muscle proprioceptors (Aim 1). We will also test the hypothesis that the sympathetic nervous system decreases muscle proprioceptor sensitivity, which may compromise motor control during chronic sympathetic over-activation (Aim 2). Finally, we will develop a tool for specific gamma motor neuron stimulation that will have many potential uses in studies of motor control physiology (Aim 3). The results from these studies will provide a better understanding of the modulation of muscle proprioceptor activity and suggest mechanisms for plasticity in the muscle proprioceptors. Additionally, this information will suggest potential targets to normalize proprioception in conditions like aging and diabetes.